Although clinical trials demonstrated that antithrombotic therapy can reduce the risk of stroke in carefully selected patients with atrial fibrillation (AF), many patients were excluded from these trials because of their advanced age, comorbid conditions, or both. Exclusion of the very elderly has led to uncertainty about the effectiveness and safety of stroke prophylaxis for patients older than 75 years. To address the shortcoming of available data, we will compare outcomes in a cohort of 3600 Medicare beneficiaries with AF who were prescribed warfarin, aspirin, or neither upon hospital discharge. In collaboration with 5 Peer Review Organizations (PROs) we will use Medicare Part A claims data to determine how prescribing antithrombotic therapy affects the rates of death, stroke, and hemorrhage. The broad, long-term objective of the proposed study is to decrease the mortality and improve the quality of life of patients who have AF. In pursuit of this dual objective, the study has 3 specific aims: (l) to determine the effectiveness of prescribing antithrombotic therapy in very elderly patients with AF; (2) to determine the safety of prescribing antithrombotic therapy in very elderly patients with AF; and (3) to conduct a formal cost-benefit analysis of prescribing antithrombotic therapy in very elderly patients with AF. To assess effectiveness, we will determine how antithrombotic therapy affects the rate of death or nonfatal stroke. To assess safety, we will determine how antithrombotic therapy affects the rate of major hemorrhage. To perform the cost-benefit analysis we will use the observed rates of death, stroke, and hemorrhage in a decision model to estimate the effect of antithrombotic therapy on quality- adjusted survival and costs. Results from our pilot study, in combination with other literature, demonstrate that the proposed project has potential to save lives, prevent strokes, and reduce health care expenditure. In our pilot study we found that the absolute reduction in death and nonfatal stroke attributable to antithrombotic therapy may be greatest in patients older than 75. If the proposed project confirms the results of the pilot study, it will clarify the risks and benefits of prescribing antithrombotic therapy to the very elderly and elucidate the optimal stroke prophylaxis for this growing population.